Ito Takamichi, Tanaka Yuka, Kaku-Ito Yumiko, Oda Yoshinao, Nakahara Takeshi
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Sci Rep. 2024 Feb 19;14(1):4048. doi: 10.1038/s41598-024-54773-8.
Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.
乳房外佩吉特病(EMPD)是一种罕见的皮肤癌,主要影响老年人,主要发生在有顶泌汗腺的部位。尽管大多数早期EMPD病变进展缓慢,但由于缺乏有效的全身治疗,转移性EMPD患者的预后较差。在本研究中,我们研究了强效转录因子叉头框M1(FOXM1)在EMPD中的作用,并评估了FOXM1作为治疗靶点的潜力。对112例原发性和17例转移性EMPD样本进行免疫组织化学分析,结果显示FOXM1表达随肿瘤进展而增加。肿瘤细胞中FOXM1表达超过10%的患者的疾病特异性生存期明显短于其他患者(p = 0.0397)。在使用我们新建立的EMPD细胞系KS-EMPD-1进行的体外研究中,我们发现FOXM1高表达。敲低FOXM1会损害肿瘤细胞的活力、迁移和侵袭能力。使用硫链丝菌素抑制FOXM1也会以剂量依赖的方式降低肿瘤细胞的活力。这些发现表明,FOXM1是EMPD患者有前景的治疗靶点。